The cholinergic system in rat testis is of non-neuronal origin

Schirmer, Sylvia; Eckhardt, I; Lau, Helene; Klein, Jochen; DeGraaf, Yvette; Lips, Katrin Susanne; Pineau, Charles; Gibbins, Ian L.; Kummer, Wolfgang; Meinhardt, Andreas; Haberberger, Rainer Viktor

doi:10.1530/rep-10-0302

Cited by 39 publications

(25 citation statements)

References 46 publications

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“…a7 is present in various non-neuronal tissues, such as glia (Sharma and Vijayaraghavan, 2001), blood cells (Kawashima and Fujii, 2004;De Rosa et al, 2005;Báez-Pagán et al, 2015), keratinocytes , epithelial cells and fibroblasts (Zia et al, 1997), endothelial cells (Macklin et al, 1998), cells of the digestive system and lung cells (reviewed in Wessler and Kirkpatrick, 2008), spermatogonia, spermatocytes, and seminiferous tubular and Sertoli cells (Schirmer et al, 2011). The functional role of a7 in these cells is being intensively investigated and has been associated with differentiation, migration, adhesion, cell contact, apoptosis, and angiogenesis processes (Ni et al, 2010;Egea et al, 2015;Zdanowski et al, 2015).…”

Section: Extraneuronal A7 and Its Pleiotropic Rolesmentioning

confidence: 99%

Understanding the Bases of Function and Modulation of α7 Nicotinic Receptors: Implications for Drug Discovery

2016

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The nicotinic acetylcholine receptor (nAChR) belongs to a superfamily of pentameric ligand-gated ion channels involved in many physiologic and pathologic processes. Among nAChRs, receptors comprising the a7 subunit are unique because of their high Ca 21 permeability and fast desensitization. nAChR agonists elicit a transient ion flux response that is further sustained by the release of calcium from intracellular sources. Owing to the dual ionotropic/metabotropic nature of a7 receptors, signaling pathways are activated. The a7 subunit is highly expressed in the nervous system, mostly in regions implicated in cognition and memory and has therefore attracted attention as a novel drug target. Additionally, its dysfunction is associated with several neuropsychiatric and neurologic disorders, such as schizophrenia and Alzheimer's disease. a7 is also expressed in non-neuronal cells, particularly immune cells, where it plays a role in immunity, inflammation, and neuroprotection. Thus, a7 potentiation has emerged as a therapeutic strategy for several neurologic and inflammatory disorders. With unique activation properties, the receptor is a sensitive drug target carrying different potential binding sites for chemical modulators, particularly agonists and positive allosteric modulators. Although macroscopic and singlechannel recordings have provided significant information about the underlying molecular mechanisms and binding sites of modulatory compounds, we know just the tip of the iceberg. Further concerted efforts are necessary to effectively exploit a7 as a drug target for each pathologic situation. In this article, we focus mainly on the molecular basis of activation and drug modulation of a7, key pillars for rational drug design.

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Section: Extraneuronal A7 and Its Pleiotropic Rolesmentioning

confidence: 99%

Understanding the Bases of Function and Modulation of α7 Nicotinic Receptors: Implications for Drug Discovery

2016

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“…In the male reproductive system, the presence of an NNCS was clearly shown for the testis, as ACh-synthesizing enzyme ChAT, transporters and ACh receptors were expressed in non-innervated testis parenchyma [158]. ChAT was also shown to be expressed in spermatozoa [159], and release of non-neuronal ACh was measured in the germinal epithelium [158].…”

Section: Reproductive Systemmentioning

confidence: 99%

“…ChAT was also shown to be expressed in spermatozoa [159], and release of non-neuronal ACh was measured in the germinal epithelium [158]. For the prostate gland, activation of mAChR results in secretion of prostate fluids [160] as well as in contractile response which is being mediated via M3 mAChR in the mouse [161].…”

Section: Reproductive Systemmentioning

confidence: 99%

The Non-Neuronal Cholinergic System in Health and Disease

Beckmann¹,

Lips²

2013

Pharmacology

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Acetylcholine (ACh) is not only a neurotransmitter but is an ancient molecule that can be released by and act on non-neuronal cells. In these cells the system of ACh-synthesizing enzymes, transporters, receptors and degrading enzymes is termed the non-neuronal cholinergic system (NNCS). There is increasing evidence that the NNCS is dysregulated in various diseases and can have an influence on their pathology. However, for many organ systems not much is known about the expression and function of the NNCS. Thus, this review focusses on the role of the NNCS in different organ systems in health and disease. Dysregulation of ACh synthesis and release, mutations or polymorphisms in genes encoding NNCS components, and auto-antibodies against NNCS components are common factors influencing disease progression. Pharmacological agents targeting the NNCS are already successfully in clinical use for some disorders, indicating that interfering with this system is very promising and more research is needed to elucidate the role of the NNCS in different tissues and pathological states.

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“…Even child exposure to environmental tobacco smoke (cotinine concentrations of ∼1 vs. >100 ng/ml in tobacco users) is associated with deficits in neurodevelopment, intelligence, attention, and academic achievement (147, 148). Cholinergic signaling also plays an important role in non-neuronal cells, including those of the immune system, lungs, gut, and testes (149, 150), so nicotine and other cholinergic toxins could disrupt their development and function as well.…”

Section: Age Differences In Drug Use: a Developmental Switch?mentioning

confidence: 99%

Explaining Human Recreational Use of ‘pesticides’: The Neurotoxin Regulation Model of Substance Use vs. the Hijack Model and Implications for Age and Sex Differences in Drug Consumption

2013

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Most globally popular drugs are plant neurotoxins or their close chemical analogs. These compounds evolved to deter, not reward or reinforce, consumption. Moreover, they reliably activate virtually all toxin defense mechanisms, and are thus correctly identified by human neurophysiology as toxins. Acute drug toxicity must therefore play a more central role in drug use theory. We accordingly challenge the popular idea that the rewarding and reinforcing properties of drugs “hijack” the brain, and propose instead that the brain evolved to carefully regulate neurotoxin consumption to minimize fitness costs and maximize fitness benefits. This perspective provides a compelling explanation for the dramatic changes in substance use that occur during the transition from childhood to adulthood, and for pervasive sex differences in substance use: because nicotine and many other plant neurotoxins are teratogenic, children, and to a lesser extent women of childbearing age, evolved to avoid ingesting them. However, during the course of human evolution many adolescents and adults reaped net benefits from regulated intake of plant neurotoxins.

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The cholinergic system in rat testis is of non-neuronal origin

Cited by 39 publications

References 46 publications

Understanding the Bases of Function and Modulation of α7 Nicotinic Receptors: Implications for Drug Discovery

Understanding the Bases of Function and Modulation of α7 Nicotinic Receptors: Implications for Drug Discovery

The Non-Neuronal Cholinergic System in Health and Disease

Explaining Human Recreational Use of ‘pesticides’: The Neurotoxin Regulation Model of Substance Use vs. the Hijack Model and Implications for Age and Sex Differences in Drug Consumption

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